These studies involve the generation, characterization, and utilization of monoclonal antibodies (MAbs) directed against antigens associated with human carcinomas. These MAbs are being used to better understand the cell biology and pathogenesis of several human carcinomas and to provide reagents that may be useful in several areas of the management of human carcinoma. These include in vitro diagnosis via serum assays and/or immunohistopathology, in vivo diagnosis such as gamma scanning, and potentially therapy. The MAbs generated can be classified into three groups based on the expression of the detected antigens. These are (a) antigens differentially expressed in human carcinoma versus normal adult tissues, such as the pancarcinoma tumor-associated glycoprotein (TAG)-72 which is detected by MAbs B72.3 and CC49, and carcinoembryonic antigen (CEA) which is detected by MAbs COL-1 through COL-15; (b) tissue-associated antigens, such as the breast associated antigen detected by MAb DF3, and the colon-associated antigen detected by MAb D612; and (c) oncogene- or retroviral-related gene products. Since MAb B72.3 has been shown to selectively target a range of carcinomas in clinical trials involving over 1000 patients, studies were conducted to characterize a series of "second generation" MAbs to the TAG-72 antigen. These studies demonstrated that some of these second generation CC MAbs, such as CC83 and CC49, have a higher affinity constant for TAG-72 than B72.3, and may be better suited that B72.3 for some clinical applications. A serologic map of TAG-72 has been constructed with 19 anti-TAG-72 MAbs. Studies have also been conducted in the analysis of the CC MAbs, COL MAbs, and MAb D612 to define which MAbs are best suited for in vivo clinical applications. Emphasis has also been placed on defining and characterizing the tumor associated antigens detected by these MAbs. Work previously reported under project numbers ZOI CB 05233 and Z01 CB 09026 have been incorporated into this project.